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1.
Chem Sci ; 15(22): 8355-8362, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38846401

ABSTRACT

Biomarkers are present in various metabolism processes, demanding precise and meticulous analysis at the single-molecule level for accurate clinical diagnosis. Given the need for high sensitivity, biological nanopore have been applied for single biomarker sensing. However, the detection of low-volume biomarkers poses challenges due to their low concentrations in dilute buffer solutions, as well as difficulty in parallel detection. Here, a droplet nanopore technique is developed for low-volume and high-throughput single biomarker detection at the sub-microliter scale, which shows a 2000-fold volume reduction compared to conventional setups. To prove the concept, this nanopore sensing platform not only enables multichannel recording but also significantly lowers the detection limit for various types of biomarkers such as angiotensin II, to 42 pg. This advancement enables direct biomarker detection at the picogram level. Such a leap forward in detection capability positions this nanopore sensing platform as a promising candidate for point-of-care testing of biomarker at single-molecule level, while substantially minimizing the need for sample dilution.

2.
Nat Plants ; 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38831046

ABSTRACT

Hybrid rice has achieved high grain yield and greatly contributes to food security, but the manual-labour-intensive hybrid seed production process limits fully mechanized hybrid rice breeding. For next-generation hybrid seed production, the use of small-grain male sterile lines to mechanically separate small hybrid seeds from mixed harvest is promising. However, it is difficult to find ideal grain-size genes for breeding ideal small-grain male sterile lines without penalties in the number of hybrid seeds and hybrid rice yield. Here we report that the use of small-grain alleles of the ideal grain-size gene GSE3 in male sterile lines enables fully mechanized hybrid seed production and dramatically increases hybrid seed number in three-line and two-line hybrid rice systems. The GSE3 gene encodes a histone acetyltransferase that binds histones and influences histone acetylation levels. GSE3 is recruited by the transcription factor GS2 to the promoters of their co-regulated grain-size genes and influences the histone acetylation status of their co-regulated genes. Field trials demonstrate that genome editing of GSE3 can be used to immediately improve current elite male sterile lines of hybrid rice for fully mechanized hybrid rice breeding, providing a new perspective for mechanized hybrid breeding in other crops.

3.
Harmful Algae ; 135: 102633, 2024 May.
Article in English | MEDLINE | ID: mdl-38830715

ABSTRACT

Nitrogen-fixing cyanobacteria not only cause severe blooms but also play an important role in the nitrogen input processes of lakes. The production of extracellular polymeric substances (EPS) and the ability to fix nitrogen from the atmosphere provide nitrogen-fixing cyanobacteria with a competitive advantage over other organisms. Temperature and nitrogen availability are key environmental factors in regulating the growth of cyanobacteria. In this study, Dolichospermum (formerly known as Anabaena) was cultivated at three different temperatures (10 °C, 20 °C, and 30 °C) to examine the impact of temperature and nitrogen availability on nitrogen fixation capacity and the release of EPS. Initially, confocal laser scanning microscopy (CLSM) and the quantification of heterocysts at different temperatures revealed that lower temperatures (10 °C) hindered the differentiation of heterocysts under nitrogen-deprived conditions. Additionally, while heterocysts inhibited the photosynthetic activity of Dolichospermum, the secretion of EPS was notably affected by nitrogen limitation, particularly at 30 °C. Finally, real-time quantitative polymerase chain reaction (qPCR) was used to measure the expression of nitrogen-utilizing genes (ntcA and nifH) and EPS synthesis-related genes (wzb and wzc). The results indicated that under nitrogen-deprived conditions, the expression of each gene was upregulated, and there was a significant correlation between the upregulation of nitrogen-utilizing and EPS synthesis genes (P < 0.05). Our findings suggested that Dolichospermum responded to temperature variation by affecting the formation of heterocysts, impacting its potential nitrogen fixation capacity. Furthermore, the quantity of EPS released was more influenced by nitrogen availability than temperature. This research enhances our comprehension of interconnections between nitrogen deprivation and EPS production under the different temperatures.


Subject(s)
Extracellular Polymeric Substance Matrix , Nitrogen Fixation , Nitrogen , Temperature , Nitrogen/metabolism , Extracellular Polymeric Substance Matrix/metabolism , Anabaena/metabolism , Anabaena/physiology , Anabaena/genetics
4.
iScience ; 27(5): 109725, 2024 May 17.
Article in English | MEDLINE | ID: mdl-38706866

ABSTRACT

The growth of environmentally sensitive complex-shaped electronic devices (ECEDs) has led to a surging demand for flexible electromagnetic wave (EMW) absorbers. Herein, the water loss property of hydrogel was ingeniously applied for the flexible encapsulation (FE) of ECEDs. To be specific, saturated state (SGT) hydrogels were prepared by chemical cross-linking, and the hydrogen bond dissipation network promoted FE. Additionally, SGT has an effective absorption bandwidth (EAB) of 6.04 GHz at 1.65 mm due to the presence of dipole polarization. With the loss of water, SGT transitions to its natural state (NGT), and the decreasing conductivity leads to better impedance matching. NGT exhibited a broader EAB (9.20 GHz at 2.65 mm) and also strength and lightness (density of 0.3 g cm-3). Furthermore, the semi-automatic reversible cyclic transformation between SGT and NGT gels further broadens application scenarios. GT gel combines self-encapsulation and self-optimized performance as a potential EMW absorber for FE.

5.
Heliyon ; 10(9): e28876, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38707353

ABSTRACT

Exposure to anesthesia in early life may cause severe damage to the brain and lead to cognitive impairment. The underlying mechanisms, which have only been investigated in a limited scale, remains largely elusive. We performed translatome and transcriptome sequencing together for the first time in hippocampus of neonatal mice that were exposed to sevoflurane. We treated a group of neonatal mice with 2.5 % sevoflurane for 2 h on day 6, 7, 8, 9 and treated another group on day 6, 7. We performed behavioral study after day 30 for both groups and the control to evaluate the cognitive impairment. On day 36, we collected translatome and transcriptome from the hippocampus in the two groups, compared the gene expression levels between the groups and the control, and validated the results with RT-qPCR. We identified 1750 differentially expressed genes (DEGs) from translatome comparison and 1109 DEGs from transcriptome comparison. As expected, translatome-based DEGs significantly overlapped with transcriptome-based DEGs, and functional enrichment analysis generated similar enriched cognition-related GO terms and KEGG pathways. However, for many genes like Hspa5, their alterations in translatome differed remarkably from those in transcriptome, and Western blot results were largely concordant with the former, suggesting that translational regulation plays a significant role in cellular response to sevoflurane. Our study revealed global alterations in translatome and transcriptome of mice hippocampus after neonatal exposure to sevoflurane anesthesia and highlighted the importance of translatome analysis in understanding the mechanisms responsible for anesthesia-induced cognitive impairment.

6.
Heliyon ; 10(10): e30803, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38770297

ABSTRACT

Background: Gastric cancer necessitates novel treatments, and exosomes are promising therapeutic carriers. We created miR-494-3p inhibitor exosomes to assess their effects on gastric cancer cells. Methods: We conducted a comprehensive investigation into the expression of the oncogenic miR-494-3p in gastric cancer tissues from patients. Subsequently, we engineered miR-494-3p inhibitor-loaded exosomes and characterized their morphology and size through transmission electron microscopy and nanoparticle tracking analysis. We next determined the encapsulation efficiency of the miR-494-3p inhibitor within these exosomes and evaluated the exosomes' structural integrity by quantifying the presence of exosomal markers. Following these validations, we co-cultured miR-494-3p inhibitor exosomes with cancer cells and employed PKH26 staining to visualize the efficient endocytosis of engineered exosomes by gastric cancer cells and assess the impact of these modified exosomes on gastric cancer cell proliferation, apoptosis, migration, and invasion. Results: Increased expression of miR-494-3p was observed in gastric cancer tissues as compared to controls. Significant low miR-494-3p levels were found within miR-494-3p inhibitor exosomes, signifying effective encapsulation. The incorporation of miR-494-3p inhibitor into engineered exosomes did not alter exosome morphology or size. Finally, PKH26-stained exosomes clearly demonstrated efficient endocytosis by gastric cancer cells, leading to reduced proliferation, migration, invasion, and increased apoptosis. Conclusion: Our study identifies elevated miR-494-3p in gastric cancer tissues prompting the development of miR-494-3p inhibitor-loaded exosomes with efficient encapsulation. These engineered exosomes demonstrate successful endocytosis by cancer cells. This highlights their potential for therapeutic use in gastric cancer treatment by suppressing proliferation, migration, and invasion while enhancing apoptosis.

7.
Braz J Med Biol Res ; 57: e13344, 2024.
Article in English | MEDLINE | ID: mdl-38808887

ABSTRACT

Reminiscence therapy (RT) attenuates psychological disorders in cancer patients. This study aimed to evaluate the effect of RT on anxiety, depression, spiritual well-being, and quality of life in elderly patients with unresectable, metastatic gastrointestinal cancer. A total of 222 elderly patients with unresectable, metastatic gastrointestinal cancer were randomized into RT group (RT plus usual care, n=112) or control group (usual care, n=110) with a 6-month intervention. Hospital Anxiety and Depression Scale for Anxiety (HADS-A) and Depression (HADS-D), Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being Scale (FACIT-Sp), and Quality of Life Questionnaire-Core 30 (QLQ-C30) were evaluated at month (M)0, M1, M3, and M6. Concerning the primary outcome, HADS-A score at M6 decreased in the RT group compared to the control group (P=0.005). As to secondary outcomes, the RT group showed decreased HADS-A scores at M3, anxiety rate at M3, HADS-D scores at M3 and M6, depression rate at M6, as well as greater FACIT-Sp scores at M1, M3, and M6 vs the control group (all P<0.050). Additionally, QLQ-C30 global health score was elevated at M1 (P=0.046) and M6 (P=0.005), functions score was greater at M6 (P=0.038), and symptoms score was lower at M3 (P=0.019) in the RT group than in the control group. Subgroup analysis revealed that the addition of RT was more effective for patients with anxiety or depression at baseline. In summary, RT alleviated anxiety and depression, and improved the spiritual well-being and quality of life within 6 months in elderly patients with unresectable, metastatic gastrointestinal cancer.


Subject(s)
Anxiety , Depression , Gastrointestinal Neoplasms , Mental Health , Quality of Life , Humans , Male , Female , Gastrointestinal Neoplasms/psychology , Gastrointestinal Neoplasms/therapy , Aged , Anxiety/therapy , Depression/therapy , Treatment Outcome , Surveys and Questionnaires , Middle Aged , Aged, 80 and over , Psychiatric Status Rating Scales , Psychotherapy/methods
8.
Nat Biomed Eng ; 2024 May 22.
Article in English | MEDLINE | ID: mdl-38778183

ABSTRACT

The functions of non-coding regulatory elements (NCREs), which constitute a major fraction of the human genome, have not been systematically studied. Here we report a method involving libraries of paired single-guide RNAs targeting both ends of an NCRE as a screening system for the Cas9-mediated deletion of thousands of NCREs genome-wide to study their functions in distinct biological contexts. By using K562 and 293T cell lines and human embryonic stem cells, we show that NCREs can have redundant functions, and that many ultra-conserved elements have silencer activity and play essential roles in cell growth and in cellular responses to drugs (notably, the ultra-conserved element PAX6_Tarzan may be critical for heart development, as removing it from human embryonic stem cells led to defects in cardiomyocyte differentiation). The high-throughput screen, which is compatible with single-cell sequencing, may allow for the identification of druggable NCREs.

9.
ACS Appl Mater Interfaces ; 16(21): 27767-27777, 2024 May 29.
Article in English | MEDLINE | ID: mdl-38752680

ABSTRACT

Electrochemiluminescence (ECL) luminophores with wavelength-tunable multicolor emissions are essential for multicolor ECL imaging detection and multiplexed analysis. In this work, silver nanoparticle (Ag NP)-decorated graphitic carbon nitride (g-CN@Ag) nanocomposites were synthesized. The morphology, chemical composition, structure, and ECL property of g-CN@Ag were investigated. The prepared g-CN, g-CN@Ag1, g-CN@Ag5, and g-CN@Ag10 can produce blue, blue-green, chartreuse, and yellow colored ECL emissions, respectively, by using K2S2O8 as the coreagent. The ECL emission wavelength of g-CN@Ag can be regulated from 460 to 565 nm by modulating the content of the immobilized Ag NPs. Then, a multicolor ECL detection array was fabricated by using g-CN, g-CN@Ag1, g-CN@Ag5, and g-CN@Ag10 as four ECL luminophores. Dopamine was detected based on its inhibition effect on the multicolor ECL emissions. The linear range is from 0.1 nM to 1 mM with the lowest detection limit of 44 pM. Then, machine learning-assisted multiparameter concentration prediction of dopamine was further carried out by combining the deep neural network (DNN) algorithm. This work provides a new avenue to regulate the ECL emission wavelength of g-CN by using the metal nanoparticle modification strategy and presents an effective machine learning-assisted multicolor ECL detection strategy for accurate multiparameter quantitative detection.

10.
Exp Cell Res ; 439(1): 114088, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38744409

ABSTRACT

Neuroinflammation mediated by microglia plays an important role in the etiology of Parkinson's disease (PD). Rho family GTPase 3 (RND3) exerts anti-inflammatory effects and may act as a potential new inducer of neuroprotective phenotypes in microglia. However, whether RND3 can be used to regulate microglia activation or reduce neuroinflammation in PD remains elusive. The study investigated the microglia modulating effects and potential anti-inflammatory effects of RND3 in vivo and in vitro, using animal models of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD and cell models of BV-2 cells stimulated by LPS plus IFN-γ with or without RND3-overexpression. The results showed that RND3 was highly expressed in the MPTP-induced PD mouse model and BV-2 cells treated with LPS and IFN-γ. In vivo experiments confirmed that RND3 overexpression could modulate microglia phenotype and ameliorate MPTP-induced neuroinflammation through inhibiting activation of the NLRP3 inflammasome in substantia nigra pars compacta (SNpc). In vitro study showed that RND3 overexpression could attenuate the production of pro-inflammatory factors in BV2 cells stimulated by LPS and IFN-γ. Mechanistically, RND3 reduced the activation of the NLRP3 inflammasome upon LPS and IFN-γ stimulation. Taken together, these findings suggest that RND3 modulates microglial polarization and alleviates neuroinflammation in Parkinson's disease by suppressing NLRP3 inflammasome activation.


Subject(s)
Inflammasomes , Mice, Inbred C57BL , Microglia , NLR Family, Pyrin Domain-Containing 3 Protein , Parkinson Disease , rho GTP-Binding Proteins , Animals , Microglia/metabolism , Microglia/pathology , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , Mice , Inflammasomes/metabolism , Male , rho GTP-Binding Proteins/metabolism , rho GTP-Binding Proteins/genetics , Parkinson Disease/metabolism , Parkinson Disease/pathology , Parkinson Disease/genetics , Neuroinflammatory Diseases/metabolism , Neuroinflammatory Diseases/pathology , Lipopolysaccharides/pharmacology , Disease Models, Animal , Cell Polarity , 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine , Inflammation/metabolism , Inflammation/pathology , Inflammation/genetics , Interferon-gamma/metabolism
11.
ACS Sens ; 2024 May 22.
Article in English | MEDLINE | ID: mdl-38776471

ABSTRACT

Ovarian cancer (OC) has the highest mortality rate among malignant tumors, primarily because it is difficult to diagnose early. Exosomes, a type of extracellular vesicle rich in parental information, have garnered significant attention in the field of cancer diagnosis and treatment. They play an important regulatory role in the occurrence, development, and metastasis of OC. Consequently, exosomes have emerged as noninvasive biomarkers for early cancer detection. Therefore, identifying cancer-derived exosomes may offer a novel biomarker for the early detection of OC. In this study, we developed a metal-organic frameworks assembled "double hook"-type aptamer electrochemical sensor, which enables accurate early diagnosis of OC. Under optimal experimental conditions, electrochemical impedance spectroscopy technology demonstrated a good linear relationship within the concentration range of 31-3.1 × 106 particles per microliter, with a detection limit as low as 12 particles per microliter. The universal exosome detection platform is constructed, and this platform can not only differentiate between high-grade serous ovarian cancer (HGSOC) patients and healthy individuals but also distinguish between HGSOC patients and nonhigh-grade serous OC (non-HGSOC). Consequently, it provides a novel strategy for the early diagnosis of OC and holds great significance in clinical differential diagnosis.

12.
Small ; : e2400756, 2024 May 06.
Article in English | MEDLINE | ID: mdl-38709225

ABSTRACT

The direct application of liquid marbles in electromagnetic wave (EMW) absorption is challenging due to their poor stability, susceptibility to gravitational collapse, and shaping difficulties. To address this issue, a novel strategy is proposed to incorporate liquid marble microstructures (NaCl/nano-SiO2) encapsulated in organic phases (Octadecane) into the rubber-matrix (SEBS) using the ultrasound-assisted emulsion blending method. The resulting NaCl/SiO2/Octadecane microstructures anchored to SEBS offer a substantial solid-liquid interface consisting of NaCl solution and SiO2. When subjected to an alternating electromagnetic (EM) field, the water molecules and polysorbate within SiO2 exhibit heightened responsiveness to the EM field, and the movement of Na+ and Cl- within these microstructures leads to their accumulation at the solid-liquid interface, creating an asymmetric ion distribution. This phenomenon facilitates enhanced interfacial polarization, thereby contributing to the material's EMW absorption properties. Notably, the latex with 16 wt% SEBS (E-3), exhibiting a surface morphology similar to human cell tissues, achieves complete absorption of X-band (fE = 4.20 GHz, RLmin = -33.87 dB). Moreover, the latex demonstrates light density (0.78 g cm-3) and environmental stability. This study not only highlights the predominant loss mechanism in rubber-based wave-absorbing materials but also provides valuable insights into the design of multifunctional wave-absorbing materials.

13.
Biomed Opt Express ; 15(4): 2078-2093, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38633070

ABSTRACT

To alleviate the ill-posedness of diffuse fluorescence tomography (DFT) reconstruction and improve imaging quality and speed, a model-derived deep-learning method is proposed by combining extended Kalman filtering (EKF) with a long short term memory (LSTM) neural network, where the iterative process parameters acquired by implementing semi-iteration EKF (SEKF) served as inputs to the LSTM neural network correction model for predicting the optimal fluorescence distributions. To verify the effectiveness of the SEKF-LSTM algorithm, a series of numerical simulations, phantom and in vivo experiments are conducted, and the experimental results are quantitatively evaluated and compared with the traditional EKF algorithm. The simulation experimental results show that the proposed new algorithm can effectively improve the reconstructed image quality and reconstruction speed. Importantly, the LSTM correction model trained by the simulation data also obtains satisfactory results in the experimental data, suggesting that the SEKF-LSTM algorithm possesses strong generalization ability and great potential for practical applications.

14.
Medicine (Baltimore) ; 103(17): e37863, 2024 Apr 26.
Article in English | MEDLINE | ID: mdl-38669385

ABSTRACT

The nutritional status is closely linked to the immune function of patients. Previous studies have demonstrated the utility of the Geriatric Nutritional Risk Index (GNRI) in assessing nutritional status. The aim of this study is to investigate the prognostic significance of GNRI in patients with gastric cancer who received immune checkpoint inhibitor (ICI) therapy. The study enrolled 89 gastric cancer patients who received different types of immune checkpoint inhibitors (ICIs) between August 2016 and December 2020, along with 57 patients who underwent chemotherapy during the same period as a control group. The GNRI cutoff point was established based on prior research. Differences in clinical and pathological features were analyzed using the Chi-square test or independent samples t-test. Univariate and multivariate analyses were used to identify prognostic factors for both progression-free survival (PFS) and overall survival (OS). Furthermore, nomograms were created to predict the likelihood of patient survival. There were 31 cases (21.2%) with GNRI < 92.00 and 115 cases (78.8%) with GNRI ≥ 92.00. Patients with low GNRI had significantly shorter PFS (21.33 months vs 28.37 months, P = .001) and OS (33.06 months vs 41.63 months, P = .001) than those with high GNRI, among all patients. Similar results were also found in patients treated with ICIs. Additionally, GNRI was identified as an independent prognostic factor. The C-index and 95% CI of the nomograms for predicting survival probabilities were 0.667 (0.600-0.735) and 0.685 (0.622-0.749), respectively. GNRI was significantly associated with survival time in patients with gastric cancer who received ICIs, patients with low GNRI had shorter PFS and OS. GNRI might be able to identify patients who might benefit from ICIs.


Subject(s)
Immune Checkpoint Inhibitors , Nutrition Assessment , Nutritional Status , Stomach Neoplasms , Humans , Stomach Neoplasms/drug therapy , Stomach Neoplasms/mortality , Immune Checkpoint Inhibitors/therapeutic use , Male , Female , Aged , Prognosis , Middle Aged , Geriatric Assessment/methods , Retrospective Studies , Aged, 80 and over , Nomograms , Risk Assessment/methods , Progression-Free Survival
15.
Noise Health ; 26(120): 14-18, 2024.
Article in English | MEDLINE | ID: mdl-38570305

ABSTRACT

OBJECTIVE: This study aimed to determine the postoperative effects of music therapy on negative emotions, pain, and inflammatory and physiological parameters in patients undergoing colonoscopic polypectomy. METHODS: Patients who underwent colonoscopic polypectomy in Funan County People's Hospital between March 2020 and June 2023 were selected as the research subjects. Patients were divided into exposure (underwent music therapy) and control (did not undergo music therapy) groups. Baseline characteristics, Self-rating Anxiety Scale (SAS) and Visual Analog Scale (VAS) scores, physiological parameters [systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR)], and inflammatory marker levels [neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), and erythrocyte sedimentation rate (ESR)] of patients before and after exposure to music were determined. The propensity score matching (PSM) method (1:1) was used to balance the baseline characteristics of the two groups. RESULTS: After PSM, the exposure group comprised 50 cases and the control group comprised 50 cases. The baseline characteristics were not significantly different between the two groups (P > 0.05). The postoperative SAS score of the exposure group was significantly lower than that of the control group (P < 0.05). Meanwhile, the postoperative VAS score of the exposure group was nonsignificantly lower than that of the control group (P > 0.05). Furthermore, the postoperative SBP, DBP, and HR levels of the exposure group were significantly lower than that of the control group (P < 0.05). The postoperative levels of NLR, PLR, and ESR were not significantly different between the exposure and control groups (P > 0.05). CONCLUSION: Music therapy exerts beneficial effects on the postoperative psychological and physiological parameters of patients undergoing colonoscopic polypectomy.


Subject(s)
Music Therapy , Music , Humans , Music Therapy/methods , Retrospective Studies , Anxiety/prevention & control , Anxiety/psychology , Music/psychology
16.
In Vitro Cell Dev Biol Anim ; 60(4): 365-373, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38564118

ABSTRACT

The present study was conducted to develop a green process that provides access to the development of Schiff base derivatives of chitosan with the heterocyclic moiety as a novel class of anti-gastric cancer agent. In the present study, we have synthesized these derivatives by reacting various pyrazoles with chitosan using CAN in PEG400. The compounds were synthesized in 20 min in excellent yield by using CAN at 5% in PEG400 at 80°C in the shortest reaction time of 20 min. The PEG400 could be efficiently recycled for the three consecutive runs. The developed compounds were tested for EGFR-TK inhibition using a Kinase-Glo Plus luminescence kinase assay kit where they exhibited significant activity revealing compound 2d as the most potent analog, while other compounds showed mild to moderate inhibitory activity. MTT assay was conducted to determine the effect of the three most potent EGFR inhibitors (2b, 2c, and 2d) on the proliferation of gastric cancer cells (SGC-7901). The results showed compound 2d as the most potent anticancer agent against SGC7901 cells. The effect of compound 2d was also quantified on the apoptosis and cell phase of SGC7901 cells using flow cytometry assay at various concentrations ranging from 0, 10, 20, and 30 µM. Results suggest that compound 2d showed significant inhibition of SGC-7901 by inducing apoptosis and arresting G0/G1 cell phase. The western blot analysis also revealed that compound 2d significantly inhibited the overexpression of EGFR in SGC-7901 cells. The study successfully demonstrated the development of N­pyrazole amino chitosan as a novel class of agent against gastric cancer via inhibition of EGFR.


Subject(s)
Antineoplastic Agents , Chitosan , ErbB Receptors , Polyethylene Glycols , Pyrazoles , Stomach Neoplasms , Humans , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Apoptosis/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Chitosan/chemistry , Chitosan/pharmacology , ErbB Receptors/antagonists & inhibitors , ErbB Receptors/metabolism , Green Chemistry Technology , Polyethylene Glycols/chemistry , Polyethylene Glycols/pharmacology , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/chemical synthesis , Protein Kinase Inhibitors/chemistry , Pyrazoles/pharmacology , Pyrazoles/chemical synthesis , Pyrazoles/chemistry , Stomach Neoplasms/drug therapy , Stomach Neoplasms/pathology
17.
Fish Shellfish Immunol ; 149: 109532, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38579977

ABSTRACT

C-type lectins (CTLs) execute critical functions in multiple immune responses of crustaceans as a member of pattern recognition receptors (PRRs) family. In this study, a novel CTL was identified from the exoskeleton of the oriental river prawn Macrobrachium nipponense (MnLec3). The full-length cDNA of MnLec3 was 1150 bp with an open reading frame of 723 bp, encoding 240 amino acids. MnLec3 protein contained a signal peptide and one single carbohydrate-recognition domain (CRD). MnLec3 transcripts were widely distributed at the exoskeleton all over the body. Significant up-regulation of MnLec3 in exoskeleton after Aeromonas hydrophila challenged suggested the involvement of MnLec3 as well as the possible function of the exoskeleton in immune response. In vitro tests with recombinant MnLec3 protein (rMnLec3) manifested that it had polysaccharide binding activity, a wide spectrum of bacterial binding activity and agglutination activity only for tested Gram-negative bacteria (Escherichia coli, Vibrio anguillarum and A. hydrophila). Moreover, rMnLec3 significantly promoted phagocytic ability of hemocytes against A. hydrophila in vivo. What's more, MnLec3 interference remarkably impaired the survivability of the prawns when infected with A. hydrophila. Collectively, these results ascertained that MnLec3 derived from exoskeleton took an essential part in immune defense of the prawns against invading bacteria as a PRR.


Subject(s)
Aeromonas hydrophila , Amino Acid Sequence , Arthropod Proteins , Gene Expression Regulation , Hemocytes , Immunity, Innate , Lectins, C-Type , Palaemonidae , Phagocytosis , Phylogeny , Sequence Alignment , Animals , Palaemonidae/immunology , Palaemonidae/genetics , Lectins, C-Type/genetics , Lectins, C-Type/immunology , Lectins, C-Type/chemistry , Arthropod Proteins/genetics , Arthropod Proteins/immunology , Arthropod Proteins/chemistry , Hemocytes/immunology , Immunity, Innate/genetics , Aeromonas hydrophila/physiology , Sequence Alignment/veterinary , Gene Expression Regulation/immunology , Gene Expression Profiling/veterinary , Base Sequence , Animal Shells/immunology , Animal Shells/chemistry
18.
Front Pharmacol ; 15: 1378292, 2024.
Article in English | MEDLINE | ID: mdl-38523637

ABSTRACT

Aldo-Keto Reductase Family 1 Member C3 (AKR1C3), also known as type 5 17ß-hydroxysteroid dehydrogenase (17ß-HSD5) or prostaglandin F (PGF) synthase, functions as a pivotal enzyme in androgen biosynthesis. It catalyzes the conversion of weak androgens, estrone (a weak estrogen), and PGD2 into potent androgens (testosterone and 5α-dihydrotestosterone), 17ß-estradiol (a potent estrogen), and 11ß-PGF2α, respectively. Elevated levels of AKR1C3 activate androgen receptor (AR) signaling pathway, contributing to tumor recurrence and imparting resistance to cancer therapies. The overexpression of AKR1C3 serves as an oncogenic factor, promoting carcinoma cell proliferation, invasion, and metastasis, and is correlated with unfavorable prognosis and overall survival in carcinoma patients. Inhibiting AKR1C3 has demonstrated potent efficacy in suppressing tumor progression and overcoming treatment resistance. As a result, the development and design of AKR1C3 inhibitors have garnered increasing interest among researchers, with significant progress witnessed in recent years. Novel AKR1C3 inhibitors, including natural products and analogues of existing drugs designed based on their structures and frameworks, continue to be discovered and developed in laboratories worldwide. The AKR1C3 enzyme has emerged as a key player in carcinoma progression and therapeutic resistance, posing challenges in cancer treatment. This review aims to provide a comprehensive analysis of AKR1C3's role in carcinoma development, its implications in therapeutic resistance, and recent advancements in the development of AKR1C3 inhibitors for tumor therapies.

19.
Front Oncol ; 14: 1307662, 2024.
Article in English | MEDLINE | ID: mdl-38525419

ABSTRACT

Background: Oxidative stress is strongly associated with the development, recurrence metastasis, and treatment of gastric cancer. It is yet unknown, though, how systemic oxidative stress levels relate to the surgically treated gastric cancer patients' clinical results. This research aims to investigate the prognostic effect of systemic oxidative stress score, also known as systematic oxidative stress score (SOS), on gastric cancer patients undergoing surgical treatment. Methods: Development of the SOS Formula through Least Absolute Shrinkage and Selection Operator LASSO Cox Regression. By using optimal cut-off values, the 466 patients included in the study had been split into high SOS and low SOS groups. Utilizing Chi-square test and the Wilcoxon rank sum test, this research examined the relationship between SOS and clinical traits. With the aid of Kaplan-Meier and COX regression analysis, the prognosis of patients with gastric cancer was examined. Results: SOS consisted of four oxidative stress-related laboratory indices. Univariate and multivariate COX regression analyses revealed that SOS, Age, CA724, Radical resection and TNM stage were crucial prognostic factors for OS, and the independent prognostic factors for PFS included Age, CA724, TNM stage and SOS. They could have their prognosis correctly predicted using a nomogram built around SOS and independent prognostic variables. Conclusion: SOS is a practical and reasonably priced tool for determining a patient's prognosis for gastric cancer. More notably, SOS is an accurate prognostic factor for patients with advanced gastric cancer who has undergone radical surgery.

20.
Rev Sci Instrum ; 95(3)2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38546295

ABSTRACT

To enhance the stability of the water-cooled double-crystal monochromator used at the BL17B beamline of the Shanghai Synchrotron Radiation Facility (SSRF), a study was conducted to optimize its cooling system's flow-induced vibration. Through simulation and experimental verification, the researchers analyzed the vibration mechanism and implemented improvement measures. The results indicate that the elastic bellows greatly amplify flow-induced vibration, transmitting it to the first-crystal. By positioning the bellows closer to the crystal, the relative pitch angular vibration of the double-crystal was reduced by 17.5%, and the roll angular vibration decreased by 6.1%. Furthermore, changing the flow rate from 3 to 2.4 l/min further diminished the relative pitch angular vibration by 6.0% and the roll angular vibration by 7.9%. By effectively reducing flow-induced vibration in the water-cooled double-crystal monochromator, equipment stability is enhanced, and the relative angular vibration of the double-crystal has been reduced. This research provides a valuable method and approach for optimizing the stability of the monochromator and related equipment.

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